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PMID:16389547

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Citation

Esposito, G, De Filippis, D, Carnuccio, R, Izzo, AA and Iuvone, T (2006) The marijuana component cannabidiol inhibits beta-amyloid-induced tau protein hyperphosphorylation through Wnt/beta-catenin pathway rescue in PC12 cells. J. Mol. Med. 84:253-8

Abstract

Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. A massive accumulation of beta-amyloid (Abeta) peptide aggregates has been proposed as pivotal event in AD. Abeta-induced toxicity is accompanied by a variegated combination of events including oxidative stress. The Wnt pathway has multiple actions in the cascade of events triggered by Abeta, and drugs that rescue Wnt activity may be considered as novel therapeutics for AD treatment. Cannabidiol, a non-psychoactive marijuana component, has been recently proposed as an antioxidant neuroprotective agent in neurodegenerative diseases. Moreover, it has been shown to rescue PC12 cells from toxicity induced by Abeta peptide. However, the molecular mechanism of cannabidiol-induced neuroprotective effect is still unknown. Here, we report that cannabidiol inhibits hyperphosphorylation of tau protein in Abeta-stimulated PC12 neuronal cells, which is one of the most representative hallmarks in AD. The effect of cannabidiol is mediated through the Wnt/beta-catenin pathway rescue in Abeta-stimulated PC12 cells. These results provide new molecular insight regarding the neuroprotective effect of cannabidiol and suggest its possible role in the pharmacological management of AD, especially in view of its low toxicity in humans.

Links

PubMed Online version:10.1007/s00109-005-0025-1

Keywords

Amyloid beta-Peptides/pharmacology; Animals; Ascorbic Acid/pharmacology; Cannabidiol/pharmacology; Cannabis/chemistry; Glycogen Synthase Kinase 3/drug effects; Glycogen Synthase Kinase 3/metabolism; Nerve Tissue Proteins/drug effects; Nerve Tissue Proteins/metabolism; Neurons/drug effects; Neurons/metabolism; PC12 Cells; Peptide Fragments/pharmacology; Phosphorylation; Rats; Signal Transduction; Thiadiazoles/pharmacology; Wnt Proteins/drug effects; Wnt Proteins/metabolism; beta Catenin/drug effects; beta Catenin/metabolism; tau Proteins

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:TAU

involved_in

GO:0010033: response to organic substance

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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